PagesOfWellbeing.com
  • Sleep Health
  • Medical News
  • Mental Health
  • Healthy Food
Medical News

How exactly does ketamine work? New research offers insight.

by admin February 11, 2025
February 11, 2025

Health

How exactly does ketamine work? New research offers insight.

Marc Duque Ramírez in the lab.

Photos by Grace DuVal

Clea Simon

Harvard Correspondent

January 27, 2025


4 min read

Anesthetic growing in popularity as game-changing therapy for severe, treatment-resistant depression 

The anesthetic ketamine has become increasingly popular as a treatment for people with severe depression that resists conventional therapies. A number of studies have documented the drug’s game-changing effects, but scientists have been unsure exactly how it works. Now, a tiny, translucent fish appears to provide important new insights.

Zebrafish, a member of the minnow family popular as a model for neuroscience research and in home aquariums, do not get depressed, exactly. However, when placed in a virtual environment that simulates the lack of forward movement, they do seem to “give up” — that is, they stop swimming.

Researchers have leveraged this behavior, which is reminiscent of persistent traits in human depression, as well as the tiny fish’s see-through body to observe how their tendency to give up changes when ketamine is introduced. In research published last month in the journal Neuron, scientists at Harvard and the Howard Hughes Medical Institute Janelia Research Campus were able to trace the drug’s interaction with an unexpected neural partner.

Alex Chen (left) and Marc Duque Ramírez study the movements of zebrafish.

As in humans, ketamine makes zebrafish “more resilient to this kind of futility,” said Alex Chen, a Ph.D. student in the Engert Lab in Harvard’s Department of Molecular and Cellular Biology and the Ahrens Lab at Janelia, who co-authored the paper.

Most research attention has focused on neurons, said Chen and co-lead author Marc Duque Ramírez, but their team found that supporting cells called astroglia were the ones in play with this fish “depression” and its treatment.

When the fish first perceive they aren’t moving, activity in the astroglia cells ramps up, and the zebrafish begin to swim harder. The astroglia eventually reach a threshold that signals the fish’s neurons to stop swimming. Ketamine, however, appears to overstimulate the astroglia, making them less sensitive. This overstimulation, which occurs through its stimulation of noradrenergic neurons that activate astrocytes (like astroglia), paradoxically calms the “giving up” response, so the fish continues to swim.

“That was definitely a surprise for us,” said Chen. “We knew these cells were involved in the behavior, and so we are wondering whether giving the fish ketamine would affect these cells after the drug is washed out. But we had no idea that the cells would react so strongly to the drug.”

“We expected it to have the opposite effect,” added Duque Ramírez, a Ph.D. student in the Griffin Graduate School of Arts and Sciences who is also in the Engert Lab.

The first 10 seconds show the larval zebrafish at rest. When the pattern changes to one simulating being stuck in place, the ketamine-treated fish struggles at first, but does not give up as easily and is less passive than an untreated fish.

Credit: Duque, Chen, Hsu, et al.

Duque Ramírez explained that the drug alters calcium levels in the cells, blocking increases that usually lead to the “giving up” trigger. “The hypothesis we have is that by causing this hyperactivation of astroglia, it somehow readjusts the system to a new homeostatic set point where it takes a lot more calcium to induce giving up.”

While the study increases understanding of how ketamine works, the light it has shed on the role of astroglia is key.

“Astroglia cells have historically been thought to play more of a passive role in the brain,” said Chen. “More recently we have seen that these cells can act as active signaling partners to neurons. What seems to happen is that the astroglia cells respond to norepinephrine, which is a transmitter that is released in times of stress or high arousal. The effect in fish is that when these astrocytes are activated by norepinephrine, they suppress swimming, and the fish give up.”

But while the reaction sheds light on how ketamine works, the insight does not appear to apply to other drugs.

“We also tested a bunch of other antidepressants,” said Duque Ramírez. “With some of the psychedelic compounds, even though we saw the same effect behaviorally, they didn’t cause this increase in astroglia in calcium. We think that this could suggest that these other drugs are working on parallel pathways, that they might eventually converge into the same targets, but that this effect was very specific to ketamine.”

“Most of the work being done right now on ketamine and other fast-acting antidepressants has focused primarily on their effects on neurons,” said Chen. “It seems possible that by ignoring these other cell types in the brain, it’s been an obstacle in how the field understands how these drugs work.”

This research was partially funded by the National Institutes of Health and the National Science Foundation.

previous post
New study maps the ‘dental deserts’ in the U.S. — and there are lots of them
next post
The brain’s gatekeepers

You may also like

Son’s diabetes diagnosis sent scientist on quest for...

June 26, 2025

Young researcher’s ALS attack plan is now a...

June 25, 2025

Wildfire smoke can harm heart and lungs even...

June 25, 2025

Miracle drugs don’t come out of nowhere

June 18, 2025

Vitamin D supplements may slow biological aging

June 17, 2025

We know exercise is good for you. Why?...

June 11, 2025

Do ultra-processed foods increase Parkinson’s risk?

June 10, 2025

New AI tool predicts biological age by looking...

June 5, 2025

‘Smoldering’ cardiovascular crisis

June 5, 2025

Tips for staying alive, decades in the making

May 23, 2025
Join The Exclusive Subscription Today And Get Premium Articles For Free

    Your information is secure and your privacy is protected. By opting in you agree to receive emails from us. Remember that you can opt-out any time, we hate spam too!

    Recent Posts

    • Son’s diabetes diagnosis sent scientist on quest for cure

      June 26, 2025
    • Young researcher’s ALS attack plan is now a no-go

      June 25, 2025
    • Wildfire smoke can harm heart and lungs even after the fire has ended

      June 25, 2025
    • Miracle drugs don’t come out of nowhere

      June 18, 2025
    • Vitamin D supplements may slow biological aging

      June 17, 2025
    • Contact us
    • Privacy Policy
    • Terms & Conditions
    • Email Whitelisting

    Copyright © 2025 PagesOfWellbeing.com All Rights Reserved.


    Back To Top
    PagesOfWellbeing.com
    • Sleep Health
    • Medical News
    • Mental Health
    • Healthy Food